口腔黏膜癌变过程中Bmi-1及P16蛋白的表达及意义

目的:了解Bmi-1及P16蛋白在口腔黏膜癌变过程中的表达情况,探讨Bmi-1-P16通路在口腔鳞癌发生发展中的作用及意义。方法::正常口腔黏膜10例、上皮异常增生31例、口腔鳞癌61例的石蜡包埋组织,采用免疫组化SP法检测Bmi-1及P16表达情况,分析二者的相关性及其临床病理学意义。结果:Bmi-1在正常口腔黏膜、上皮异常增生及OSCC组织中的阳性率分别为0%、29%(9/31)和62.3%(38/61);P16在正常、上皮异常增生及OSCC组中的阳性率分别为100%(10/10)、77.4%(24/31)和47.5%(29/61)。OSCC中Bmi-1阳性率在P16阴性组高于P16阳性组,差异有统计学意义(P<0.05),Spearman相关分析显示两者间具负相关关系(r=-0.414,P<0.05)。Bmi-1阳性表达及Bmi-1高表达且P16失表达与OSCC临床分期及淋巴结转移密切相关(P<0.05)。结论:Bmi-1过表达是口腔黏膜癌变过程中的早期事件,口腔鳞癌中Bmi-1过表达可能与P16失表达有关并与临床分期及淋巴结转移密切相关,有可能作为临床评估口腔鳞癌浸润、转移和预后的参考指标之一。

Expression and Significance of Bmi-1 and P16 in Oral Carcinogenesis.

Objective: To investigate the expression of Bmi-1 and P16 proteins in oral precancerous lesions and oral squamous cell carcinomas (OSCC), and elucidate their possible roles pathway in oral carcinogenesis.Methods: The tissues of 10 cases of normal oral epithelium, 31 cases of different-degree epithelium dysplasia and 61 cases of OSCC with different differentiation were collected and investigated for the expression of Bmi-1 and P16 proteins by using immunohistochemistry. The clinical and pathological significance of Bmi-1 over-expression in oral carcinogenesis was statistically analyzed by SPSS11.5.Results: The percentages of positive staining for Bmi-1 were 0 % in normal oral mucosa, 29% (9/31) in epithelial dysplasia and 62.3% (38/61) in OSCC, respectively. The percentages of positive staining for P16 were 100% (10/10) in normal oral mucosa, 77.4% (24/31) in epithelial dysplasia and 47.5% (29/61) in OSCC, respectively. The percentage of Bmi-1 over-expression with negative P16 staining in OSCC was significantly higher than that in OSCC with positive P16 staining (P<0.05), and there was a negative correlation between the expression of Bmi-1 and P16 in OSCC (r=-0.414, P<0.05). In addition, the over-expression of Bmi-1 and low-expression of P16 were positively correlated with TNM stage and lymph node metastasis in OSCC (P<0.05).Conclusion: Up-regulation of Bmi-1 was an early event in oral carcinogenesis, and might be caused by the down-regulation of P16 in OSCC, closely correlated with TNM stage and lymph node metastasis. Bmi-1 could be used as a marker for assessing the progression and prognosis of OSCC patients.